Potency of Artocarpus Heterophyllus Leaves Extract as an Antiviral against SARS-CoV-2

Natural products, particularly those derived from plants, represent a valuable source of bioactive compounds with potential antiviral activity. In this study, we investigated the antiviral activity of Indonesian plants which belong to Artocarpus genus against SARS-CoV-2 using bioassay-guided separation. Plant materials from the Artocarpus genus were successively extracted using hexane, dichloromethane, and methanol, and the antiviral activities were tested against early SARS-CoV-2 variants. Viral inhibition and cytotoxicity were assessed using RT-qPCR, plaque assays, and MTT assays. Among 54 extracts obtained from the leaves and stem bark of 10 species of Artocarpus, four dichloromethane leaf extracts inhibited viral RNA replication and cytopathic effect at a concentration of 10 μg/mL, and did not show cytotoxic effects at a concentration of 100 μg/mL. The most potent extract was dichloromethane leaf extract of Artocarpus heterophyllus (E16) with the 50% inhibitory concentration (IC₅₀) value of 2.46 µg/mL. Separation by vacuum liquid chromatography and open column chromatography yielded E16F4.3 and E16F4.4 which possess potential activity against SARS-CoV-2 with IC₅₀ values of 0.43 µg/mL and 0.28 µg/mL. These subfractions showed less cytotoxicity, with 50% cytotoxic concentration (CC₅₀) values >100 µg/mL. The selective index (SI; CC₅₀/IC₅₀) of E16F4.3 and E16F4.4 were >232.6 and >357.1, respectively. These results indicate that the leaf extract of Artocarpus heterophyllus contains promising drug candidates against SARS-CoV-2.